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Published on: March 12, 2018
Identification of Osteosarcoma Metastasis-Associated Gene Biomarkers and Potentially Targeted Drugs Based on
Ming-De Cao1, Yan-Cheng Song2, Zhong-Meng Yang1
1Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, Guangdong, People's Republic of China.
Background:
Metastasis is the leading cause of death for patients with osteosarcoma (OS). In the present study, we explore the biomarkers for metastatic OS and provide potential therapeutic approaches.
Materials And Methods:
RNA-Seq data and clinical follow-up information were downloaded from TARGET and GEO databases. A Cox regression model was used to analyze metastatic events. L1000FWD, DGIdb, and CMap databases were used to identify potential drugs related to metastasis. Invasion and migration transwell assays and an adhesion assay were used to identify biological functions of genes.
Results:
A total of 15 metastasis-related signatures (MRSs) were associated with the prognosis based on the TARGET or GSE21257 cohorts, among which IL10RA and TLR7 genes were especially significant. In the DGIdb drug-gene interaction database, TLR7 and IFNGR1 were found to have potential interactions with drugs. After inhibiting the expression of TLR7, the migration, invasion, and adhesion ability of OS cells were significantly enhanced, which further promoted metastasis.
Conclusion:
We identified a set of MRS that may be related to OS metastases. Among them, TLR7 plays a vital role and may be a potential target for OS metastasis treatment.
Insights
Metastasis remains a major cause of death in osteosarcoma (OS). This study identifies metastasis-related signatures (MRSs) and highlights TLR7 as a potential therapeutic target for OS metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Metastasis is the primary cause of mortality in osteosarcoma (OS) patients.
- Identifying biomarkers and therapeutic strategies for metastatic OS is crucial.
Purpose of the Study:
- To explore biomarkers associated with metastatic osteosarcoma.
- To identify potential therapeutic targets for osteosarcoma metastasis.
Main Methods:
- Utilized RNA-Seq data from TARGET and GEO databases.
- Employed Cox regression for metastatic event analysis.
- Screened drug-gene interactions using L1000FWD, DGIdb, and CMap databases.
- Performed transwell and adhesion assays to assess gene functions.
Main Results:
- Identified 15 metastasis-related signatures (MRSs) linked to prognosis in OS cohorts.
- Highlighted TLR7 and IL10RA as significant genes.
- Discovered potential drug interactions with TLR7 and IFNGR1.
- Inhibition of TLR7 enhanced OS cell migration, invasion, and adhesion, promoting metastasis.
Conclusions:
- A set of MRSs potentially related to OS metastasis was identified.
- TLR7 plays a critical role and represents a promising therapeutic target for osteosarcoma metastasis.
